The proposed work will be devoted to studies of the role of polyamines in cell growth and the means by which polyamine biosynthesis is controlled. It is known that polyamines are ubiquitous components of mammalian cells and that the formation and accumulation of these compounds, particularly spermidine, is enhanced in a wide variety of situations in which hypertrophy or hyperplasia is produced. Also, the enzymes responsible for the formation of spermidine and its precursor putrescine show rapid changes in activity in response to various stimuli and very rapid decreases in activity after inhibition of protein synthesis. These findings suggest that studies of these enzymes might provide a useful model for investigation of protein turnover which could be used even in isolated perfused organs where the organ can be maintained in a good physiological state for only a few hours. These problems will be investigated by 1) studies of the enzymes involved in polyamine biosynthesis with particular reference to purification of S-adenosyl-methionine and ornithine decarboxylases by affinity chromatography and measurement of the rate of synthesis and degradation of these enzymes by direct studies of the incorporation of labelled amino acids into the enzyme protein. 2) Studies of the further metabolism of the polyamines including measurements of the formation of acetyl and glutathionyl derivatives under a variety of physiological conditions. 3) Studies of the effects of inhibitors of polyamine synthesis such as methylglyoxal bis (guanyl-hydrazone) on cell growth. BIBLIOGRAPHIC REFERENCES: D.E. Rannels, A.E. Pegg and S.R. Rannels, (1976) Starvation results in decreased initiation factor activity in rat skeletal muscle. Biochem. Biophys. Res. Commun., in press.